Leishmaniasis and tumor necrosis factor alpha antagonists in the Mediterranean basin. A switch in clinical expression

• Published in: PLoS neglected tropical diseases 2019-08, Vol.13 (8), p.e0007708-e0007708
• Main Authors: Bosch-Nicolau, Pau, Ubals, Maria, Salvador, Fernando, Sánchez-Montalvá, Adrián, Aparicio, Gloria, Erra, Alba, Martinez de Salazar, Pablo, Sulleiro, Elena, Molina, Israel
• Format: Article
• Language: English
• Subjects: Activation; Adalimumab; Adolescent; Adult; Aged; Aged, 80 and over; Antagonists; Arthritis; Biology and Life Sciences; Blockage; Bone marrow; Care and treatment; Case studies; Child; Cutaneous leishmaniasis; Cytokines; Dermatology; Drug therapy; Drugs; Etanercept; Female; Gene expression; Genetic aspects; Golimumab; Hospitals; Humans; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - adverse effects; Infection; Infections; Infectious diseases; Infliximab; Injections, Intramuscular; Leishmaniasis; Leishmaniasis - epidemiology; Leishmaniasis - pathology; Literature reviews; Male; Medical research; Medicine and Health Sciences; Mediterranean Region - epidemiology; Middle Aged; Miltefosine; Monoclonal antibodies; Mucocutaneous leishmaniasis; Necrosis; Neoplasms; Parasites; Parasitic diseases; Patients; Polymerase chain reaction; Recurrence; Retrospective Studies; Risk analysis; Risk factors; Supervision; Surgery; Systematic Reviews as Topic; Therapy; Tropical diseases; Tumor necrosis factor; Tumor necrosis factor inhibitors; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Tumors; Vector-borne diseases; Viral infections; Visceral leishmaniasis; Young Adult
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0007708

Tumor necrosis factor alpha (TNF-α) blockers are recognized as a risk factor for reactivation of granulomatous infections. Leishmaniasis has been associated with the use of these drugs, although few cases have been reported. We performed a retrospective observational study including patients with confirmed leishmaniasis acquired in the Mediterranean basin that were under TNF-α blockers therapy at the moment of the diagnosis. Patients diagnosed in our hospital from 2008 to 2018 were included. Moreover, a systematic review of the literature was performed and cases fulfilling the inclusion criteria were also included. Forty-nine patients were analyzed including nine cases from our series. Twenty-seven (55.1%) cases were male and median age was 55 years. Twenty-five (51%) patients were under infliximab treatment, 20 (40.8%) were receiving adalimumab, 2 (4.1%) etanercept, one (2%) golimumab and one (2%) a non-specified TNF-α blocker. Regarding clinical presentation, 28 (57.1%) presented as cutaneous leishmaniasis (CL), 16 (32.6%) as visceral leishmaniasis (VL) and 5 (10.2%) as mucocutaneous leishmaniasis (MCL). All VL and MCL patients were treated with systemic therapies. Among CL patients, 13 (46.4%) were treated with a systemic drug (11 received L-AmB, one intramuscular antimonials and one miltefosine) while 14 (50%) patients were given local treatment (13 received intralesional pentavalent antimonials, and one excisional surgery). TNF-α blockers were interrupted in 32 patients (65.3%). After treatment 5 patients (10.2%) relapsed. Four patients with a CL (3 initially treated with local therapy maintaining TNF-α blockers and one treated with miltefosine) and one patient with VL treated with L-AmB maintaining TNF-α blockers. This data supports the assumption that the blockage of TNF-α modifies clinical expression of leishmaniasis in endemic population modulating the expression of the disease leading to atypical presentations. According to the cases reported, the best treatment strategy would be a systemic drug and the discontinuation of the TNF-α blockers therapy until clinical resolution.